Hepatitis C: Beyond the Basics (FL INITIAL Autonomous Practice - Differential Diagnosis)

Hepatitis C is a ribonucleic acid (RNA) virus that infects the liver. The hepatitis C virus (HCV) was isolated and identified in 1989 (Houghton, 2019). Before that, there was a strong suspicion of the presence of another hepatitis virus, aside from hepatitis A (HAV) and hepatitis B (HBV), that was causing hepatitis, and these cases were called non-A/non-B hepatitis (Houghton, 2019). (Note: Hepatitis means liver inflammation. Many viruses can cause hepatitis, hepatitis can be an autoimmune disease, and drugs and toxins can cause hepatitis).

HCV is a significant U.S. public health problem and the most commonly reported bloodborne infection in the U.S. (Kaufman et al., 2021). In 2021, there were 39.8 new cases of chronic HCV per 100,000 (Centers for Disease Control and Prevention [CDC], 2023a), and the number of acute HCV cases increased by 129% from 2014 to 2021 (CDC, 2023c). The incidence of chronic cases has decreased. In 2020, it was 40.7 (CDC, 2022), but acute cases have increased, and 65% to 85% of patients who have acute HCV develop chronic HCV (Friedman, 2024a; Martinello et al., 2023).

Targeted screening and highly effective direct-acting antiviral drugs (DAAs) have decreased the incidence of chronic HCV infections, and these drugs have a cure rate of ≥ 95% (Martinello et al., 2023). Still, testing and drug therapy must be done to be effective, and there is evidence that the efforts to do that, for many reasons, have not been consistent. Wester et al. (2023) analyzed data from > 1.7 million American adults who had had an HCV infection. The authors concluded that there is a need for more access to diagnosis, treatment, and prevention resources, and there were ". . . substantial gaps in cures nearly a decade since highly effective direct-acting antiviral (DAA) agents" (Wester et al., 2023). The well-publicized opioid epidemic.

has contributed to the number of HCV infections in the U.S. (Park et al., 2023), and people who have a substance use disorder (SUD) are less likely to receive DAA therapy (Park et al., 2023).

Note: The primary focus of this module is chronic HCV.

A 57-year-old male made an appointment with his primary care physician. The patient has no specific complaints or problems. However, he will be starting a new job that requires strenuous activity, and his employer has requested that a physician examine him to determine if he can tolerate this level of physical stress.

He is in good health, has no major medical problems, has no history of psychiatric illnesses, and does not take any prescription medications. He is moderately overweight (BMI of 27.6), drinks alcohol (occasionally to excess), and smokes one pack of cigarettes a day.

During the interview, the man admitted that as a young man, he had used intravenous (IV) drugs – heroin and occasionally cocaine ─ for a brief period but had not used any illicit substances for over 35 years. Laboratory tests reveal that his serum aspartate aminotransferase (AST) is 115 international units (IU)/liter (L), and his serum ALT is 190 IU/L; these levels are considered moderate elevations, and there are no previous tests for comparison. A test for hepatitis C antibodies is positive, and hepatitis C RNA is detected, genotype 1a. A fibroscan of his liver reveals a mild level of fibrosis but no cirrhosis. He does not have human immunodeficiency virus HIV, hepatitis A, or hepatitis B infection, and his complete blood count (CBC), international normalized ratio (INR), prothrombin time, vitamin D level, thyroid studies, and renal function tests were normal. His serum cholesterol is mildly elevated. The office screening test does not reveal the presence of or risk for depression.

The physician tells the patient it is likely that he has had hepatitis C for many years, and because he is overweight, occasionally drinks to excess, and smokes, he is at risk for progression to cirrhosis and possibly liver cancer. The physician recommends treatment with antiviral therapy, and the patient agrees. She prescribes ledipasvir/sofosbuvir (Harvoni®) one tablet a day for 12 weeks. The patient is advised that he may experience minor side effects such as diarrhea, fatigue, headache, insomnia, and nausea but that most patients tolerate the drug very well, and discontinuation because of adverse effects is very uncommon. He is enrolled in a smoking cessation program, provided with a weight reduction diet and an exercise program, and advised to stop drinking alcohol. He is also counseled on safe sex practices, given information on how HCV is transmitted, and instructed on how to avoid transmitting the virus. The physician stresses the importance of adherence to the drug regimen. The patient is instructed to contact the physician if he has any intolerable or unusual signs or symptoms, especially if he develops symptoms indicative of liver damage, e.g., ascites and jaundice.

After four weeks of drug therapy, there is no detectable HCV RNA, and the liver transaminases are within normal limits. Aside from occasional episodes of nausea, the patient has no somatic complaints, and his mood is good. Twelve weeks after finishing the drug regimen, there is no detectable HCV RNA, and his liver transaminases and all other blood tests are within normal limits. The patient has a sustained virologic response (SVR), and because his risk profile is low, the physician informs the patient that he is effectively cured; the risk of a relapse is very, very low. He is encouraged to continue with lifestyle modifications, continue safe sex practices, and continue to avoid behaviors that may put him at risk for reinfection. Because he had only mild fibrosis and no evidence of cirrhosis, no specific follow-up testing is needed.

HCV is transmitted by exposure to infected blood (CDC, 2023b; Friedman, 2024a). This can happen in many ways: blood transfusion, body piercing, during pregnancy and childbirth, healthcare exposures/patients and healthcare personnel, hemodialysis, IV drug use, household contact, e.g., sharing toothbrushes or razor, sharing needles and injection equipment during IV drug use, organ transplantation, unprotected sex, and tattooing (CDC, 2023b; Dienstag, 2022a; Friedman, 2024a). People who are homeless, immunosuppressed, incarcerated, hemophiliacs treated with clotting factors before 1987, people who had a blood transfusion or organ transplantation before July 1992, healthcare and emergency medical services personnel, people who have an HIV infection, and patients who have been recipients of blood or an organ that is infected with HCV have a higher than average risk of HCV infection (Dienstag, 2022a; Friedman, 2024a). In many cases, the transmission mode cannot be identified (Friedman, 2024a; Pfaender et al., 2018).

An HCV infection begins with acute exposure, and acute exposure is followed by one of three outcomes.

1. Acute infection and spontaneous viral clearance: Between 15% to 35% of people who have an acute HCV infection will have spontaneous clearance of the virus (Friedman, 2024a; Liu & Kao, 2023; Martinello et al., 2023). Children whose mothers had HCV infection have a spontaneous clearance rate of 25% to 40% by age three (Ades et al., 2023). Spontaneous clearance is more likely in female patients (Martinello et al., 2023; Negro, 2020; World Health Organization [WHO], 2023), young patients (Martinello et al., 2023; WHO, 2023), patients who have genotype 1 (WHO, 2023), and patients who have acute hepatitis with jaundice (Martinello et al., 2023; WHO, 2023). Spontaneous clearance does not confer immunity and HCV reinfection can happen (WHO, 2023).
2. Fulminant hepatitis and liver failure can occur, but these are very rare (Liu & Kao, 2023; Martinello et al., 2023; Odenwald & Paul, 2022).
3. Chronic infection: Most people who have asymptomatic HCV infection will not have spontaneous viral clearance, and they will develop a chronic infection (Kumar, 2022; Tada et al., 2019). Chronic HCV infection is a progressive disease, and patients can develop cirrhosis, fibrosis, and hepatocellular carcinoma or HCC (Butt et al., 2021; Dienstag, 2022b; Friedman, 2024a; Negro, 2020; Odenwald & Paul, 2022; Tada et al., 2019). These complications often occur decades after the initial infection (Kumar, 2022). Still, the natural history of chronic hepatitis C is not well characterized (Tada et al., 2019) and is very variable (Negro, 2020), particularly in terms of when these serious complications may occur. The incidence of these complications is not insignificant (Butt et al., 2021; Negro, 2020, Tada et al., 2019), and chronic HCV infection is a major cause of cirrhosis and HCC (Tada et al., 2019). In addition, chronic hepatitis C causes multiple different extrahepatic complications (Dienstag, 2022a).

The American Association for the Study of Liver Diseases (AASLD) and The Infectious Diseases Society of America (IDSA) recommend universal hepatitis C screening (Bhattacharya et al., 2023). Screening should be done with anti-HCV antibody testing and ". . . with reflex HCV RNA testing to establish the presence of active infection (as opposed to spontaneous or treatment-induced viral clearance)" (Bhattacharya et al., 2023). The United States Preventive Services Task Force (USPSTF) recommends one-time testing with an anti-HCV antibody test, followed by confirmatory polymerase chain reaction testing for asymptomatic adults aged 18 to 79 years, including pregnant persons without liver disease (USPSTF, 2020). The USPSTF also recommends that HCV screening should be considered for persons < 18 years of age and persons > 79 years of age who have a high risk of infection, e.g., current or past IV drug use (USPSTF, 2020).

(Note: Polymerase chain reaction test detects HCV RNA. Reflex HCV RNA testing is a test for the presence of HCV RNA that is done if the anti-HCV antibody test is positive.)

Screening is an important public health tool. Acute and chronic HCV infections often do not cause symptoms worldwide (Tsai et al., 2023); in the U.S. (Kasting et al., 2022; Veeramachaneni et al., 2021), many infected people do not know they are infected, and screening level is often sub-optimal (Tsai et al., 2023). Screening increases the number of cases, and the AASLD/IDSA Guidelines state, "Universal screening is a crucial and necessary component of any HCV elimination strategy because it is the entry point into the HCV continuum of care" (Bhattacharya et al., 2023).

Hepatitis C is diagnosed by testing for HCV RNA and anti-HCV antibodies (Feld, 2022); serum transaminases should also be measured. Genotype testing can be done, and it is reasonable to do so but not necessary (Feld, 2022). (Note: Genotyping and its impact on DAA therapy regimens will be discussed in the treatment section. Patients who have signs and symptoms of HCV infection and/or have had high-risk exposure should be tested.

The laboratory testing procedure for acute hepatitis C diagnosis is outlined below (Feld, 2022).

1. HCV RNA positive and anti-HCV antibody is positive – The patient has an acute or chronic infection. If the RNA or antibody tests were negative in the prior six months, the patient has an acute infection. If the RNA or antibody tests were not negative in the prior six months and the patient has had a recent high-risk exposure or a fluctuating HCV RNA test of > 1 log when the test is repeated, the patient likely has an acute infection. If that risk factor and that laboratory test result are not present, the patient likely has a chronic infection.
2. HCV RNA positive and anti-HCV antibody is negative – The patient has an acute infection.
3. HCV RNA negative and anti-HCV antibody is positive – The HCV RNA should be remeasured in 12 weeks. If the repeat HCV RNA is positive, the patient has an acute infection. If the repeat HCV RNA test is negative, the patient had an infection, but it was cleared.
4. HCV RNA negative and anti-HCV antibody is negative – An infection is unlikely.

Hepatitis C RNA can be detected within several days (Dienstag, 2022a; Feld, 2022), one to two weeks (Liu & Kao, 2023; National Clinician Consultation Center, 2021), and up to eight weeks (Feld, 2022) after an exposure. Anti-HCV antibodies can usually be detected within eight to 11 weeks (National Clinician Consultation Center, 2021), and seroconversion occurs in most patients within two to six months after exposure (Feld, 2022). Hemodialysis patients, patients who have an HIV infection, patients who are going through organ transplantation, or who are severely immunocompromised may not produce a measurable level of anti-HCV antibodies (Feld, 2022) or seroconversion may take up to a year (Liu & Kao, 2023). The results of anti-HCV-antibody testing must be interpreted carefully. A positive anti-HCV antibody test indicates the presence of the antibodies, but it may reflect:

1. An infection that was spontaneously cleared or
2. An acute or early chronic infection.

A negative test can occur if a patient has been infected, but spontaneous clearance occurs, and the antibody level goes below the detectable limit (Feld, 2022).

This section and the next will discuss the process of diagnosing chronic HCV and the evaluation of patients who have chronic HCV. Patient selection to determine who should be tested for the presence of hepatitis C was discussed in the screening section.

The diagnostic process has two components:

1. Anti-HCV antibody and HCV RNA testing, and
2. Measuring serum transaminases and blood tests like INR that reflect liver function (Abu-Freha et al., 2022; Chopra & Arora, 2024b; Liu & Zucker, 2022).

The second component can be done at the clinician's discretion.

If the anti-HCV antibody test is negative, the patient does not have chronic HCV (Chopra & Arora, 2024b). However, HCV RNA testing should be done for hemodialysis patients, patients who have an HIV infection, patients who are severely immunocompromised, and transplant patients (Chopra & Arora, 2024b), even if the anti-HCV antibody test was negative, as these patients may have a false-negative antibody test (Chopra & Arora, 2024b).

If the anti-HCV antibody test and the HCV RNA test are positive, the patient likely has chronic HCV (Chopra & Arora, 2024b). Positive results on both tests could be caused by an acute infection (Chopra & Arora, 2024b), and this has important implications, e.g., waiting to see if spontaneous viral clearance occurs or beginning the process of DAA therapy. In this situation, clinicians must take a good medical history, particularly of patient risk factors and possible exposures, and the patient's recent state of health, and carefully review any previous laboratory test results.

If the anti-HCV test is positive and the HCV RNA is negative, the patient does not have chronic hepatitis C: They had an infection, and there was viral clearance (Chopra & Arora, 2024b). False negatives and false positives can occur (Chopra & Arora, 2024b), like transfusion with blood that has anti-HCV antibodies and an HCV RNA level that is below the detection limit of the test.

Extrahepatic complications are common in patients infected with HCV (Ružić et al., 2023), and essentially every organ system can be affected (Faccioli et al., 2021; Garg et al., 2024; Mazzaro et al., 2021; Songtanin & Nugent, 2022).

Patients who have acute hepatitis C should be treated with DAA therapy unless there is a contraindication to doing so (Ghany et al., 2020; Dienstag, 2022b; Feld, 2022), and waiting for spontaneous recovery and viral clearance is not recommended (Ghany et al., 2020; Feld, 2022; Dienstag, 2022b). Primary reasons for this recommendation are:

1. Patients who have acute hepatitis C and develop chronic hepatitis C – a not insubstantial risk ─ may be lost to follow-up,
2. They may transmit HCV,
3. There is always the potential that a severe HCV infection may occur (Feld, 2022), and
4. Withholding treatment is a missed chance to prevent progression of fibrosis and the development of complications (Dienstag, 2022b).

Treatment should begin as soon as possible or when viremia is found (Feld, 2022). The recommended treatment regimen for a patient who has acute hepatitis C is the same one that is used to treat non-cirrhotic patients who have chronic hepatitis C and who are treatment-naive (Bhattacharya et al., 2023; Dienstag, 2022b; Feld, 2022). This treatment regimen is called the simplified algorithm for HCV treatment, more formally, the Simplified HCV Treatment for Treatment-Naive Adults Without Cirrhosis (Ghany et al., 2020; Bhattacharya et al., 2023). The regimen will be covered in the section Chronic Hepatitis C: Treatment. It can be viewed here.

Pre-treat evaluation and testing, monitoring during DAA therapy, and post-treatment evaluation for this patient population are the same as for patients who have chronic hepatitis C, and those topics will be discussed in the Chronic Hepatitis C section.

Ineligibilities for this treatment regimen are listed in Table 7 (Ghany et al., 2020).

Patients who are not treated should be evaluated at the six-month point to determine if they have chronic HCV (Feld, 2022). If spontaneous clearance occurs, it usually happens within 12 weeks; if a patient wants to forgo treatment and wait for 12 weeks, remeasure the HCV RNA level, and if needed, treatment can be done then (Feld, 2022).

There are three types of DAAs: NS3/4A protease inhibitors, NS5B polymerase inhibitors, and NS5A protein inhibitors (Kiser, 2023). The DAAs eliminate HCV by inhibiting viral growth, viral replication, and viral maturation (Kiser, 2023). The NS3/4A protease inhibitors inhibit an enzyme that is involved in viral replication (Kiser, 2023). The NS5B drugs affect the function of an enzyme that HCV needs to synthesize RNA (Kiser, 2023).

The latest DAAs are very effective, safe, and well-tolerated (Bhattacharya et al., 2023), the duration of treatment is brief compared to the older interferon-based therapy, and viral clearance is > 95% (Dienstag, 2022b; Martinello et al., 2023). HCV has been called the only chronic viral infection that can be cured (Pol & Lagave, 2019).

There are multiple DAA treatment regimens: The regimens are prescribed based on genotype and the presence or absence of cirrhosis and hepatic decompensation (Ghany et al., 2020). These treatment regimens are designed for patients who have chronic HCV and who have not been previously treated with a DAA, interferon, peginterferon, and/or ribavirin (Ghany et al., 2020).

Most patients are eligible for one of the two simplified regimens: 1) Simplified Pangenotypic HCV Treatment for Treatment-Naïve Adults without Cirrhosis, and 2) Simplified Pangenotypic HCV Treatment for Treatment-Naïve Adults With Compensated Cirrhosis (Ghany et al., 2020).

The pretreatment recommendations, recommendations for patient monitoring during DAA therapy, and the recommendations for post-treatment assessment and follow-up are essentially the same for both variations of the Simplified Pangenotypic HCV Treatment for Treatment-Naïve Adults, without and with compensated cirrhosis.

In the treatment regimen for patients who have compensated cirrhosis, the eligibility and non-eligibility requirements and the pretreatment assessment recommendations are slightly different.

The AASLD/IDSA simplified treatment guidelines state that if the patient is positive for hepatitis B surface antigen (HBsAg), acute or chronically infected, direct-acting antivirals are contraindicated (Ghany et al., 2020). Chopra & Pockros (2024) recommend that if the HBsAg is positive and the patient meets the treatment criteria, HBV antiviral therapy should be started (Chopra & Pockros, 2024).

For patients who have HCV and HIV infection, the DAAs are safe and effective (Ghany et al., 2020; Rockstroh, 2024), and the SVR that is attained is comparable to that of patients who have HCV infection alone (Ghany et al., 2020; Rockstroh, 2024).

A simplified treatment program for HCV/HIV co-infection has been successfully used and is recommended (Rockstroh, 2024): glecaprevir/pibrentasvir for eight weeks or sofosbuvir/velpatasvir for 12 weeks. If the patient has genotype C and has cirrhosis, administer glecaprevir/pibrentasvir for eight weeks (Rockstroh, 2024). If the patient has decompensated cirrhosis, a specialist should be consulted (Rockstroh, 2024). If a patient is not receiving anti-retroviral therapy (ART), wait four to six weeks before beginning ART (Rockstroh, 2024).It is very important to check for drug-drug interactions before starting DAA therapy in patients who have an HIV infection (Ghany et al., 2020).

There is very little information on the use of DAAs during pregnancy (Ghany et al., 2020). Women of childbearing age who have hepatitis C and who are not pregnant should be informed of the benefits of DAA therapy, and if they become infected during pregnancy, the risks and benefits of DAA therapy should be considered on a case-by-case basis (Ghany et al., 2020).

Pregnant women should be tested for hepatitis C (Ghany et al., 2020). If the patient has a positive HCV antibody test, HCV RNA and routine liver function tests should be done (Ghany et al., 2020).

Pregnancy does not seem to influence the course of HCV infection (Ghany et al., 2020). Serum transaminases do rise, peak in the third trimester, and return to normal after birth. Some patients develop intrahepatic cholestasis of pregnancy, aka ICP (Ghany et al., 2020), a condition that has been associated with adverse fetal and maternal outcomes (Ghany et al., 2020; Hobson et al., 2022). If the patient has jaundice or pruritus, ". . . there should be a high index of suspicion for intrahepatic cholestasis of pregnancy . . .  ; all patients with this syndrome should be immediately referred to a high-risk obstetrical specialist for monitoring and treatment" (Ghany et al., 2020).

During perinatal care and delivery, diagnostic testing should be done by amniocentesis, not chorionic villus sampling, and episiotomies, internal fetal monitoring, and prolonged membrane rupture should be avoided (Ghany et al., 2020).

The use of DAAs and specific DAAs to treat patients who have chronic hepatitis C and decompensated cirrhosis, Child-Pugh class B or C, is controversial. In 2019, the U.S. Food & Drug Administration (FDA) issued a warning stating that rare cases of serious liver injury had occurred in patients who had advanced liver disease and had been treated with Mayvret® (glecaprevir and pibrentasvir), Vosevi® (sofosbuvir, velpatasvir, and voxilaprevir), and Zepatier® (elbasvir and grazoprevir)(FDA, 2019). The prescribing information for these drugs states that hepatic decompensation/failure had been reported in patients who had Child-Pugh class B or C who had been treated with HCV NS3/4A protease inhibitors, e.g., glecaprevir, grazoprevir, voxilaprevir. The AASLD/IDSA recommends referring these patients to a specialist, ideally in a liver transplant center (Ghany et al., 2020). According to the AASLD/IDSA, most patients who have decompensated cirrhosis and who receive DAA therapy do have clinical and laboratory evidence of improvement, the rate of SVR is less than in patients without decompensated cirrhosis, and DAA therapy may or may not improve the risk of complications and long-term survival (Ghany et al., 2020). Information on the topic, including recommended DAA regimens, can be viewed on the AASLD/IDSA HCV website here.

DAAs have been shown to prevent HCC in patients who have hepatitis C (Ito & Nguyen, 2023), including patients who have decompensated cirrhosis (Ito & Nguyen, 2023). They are also safe and effective for patients who have HCC (Ito & Nguyen, 2023), and DAA does not increase the risk of HCC incidence or recurrence (Chopra & Arora, 2024b; Ito & Nyguen, 2023). Treatment of HCC caused by HCV should be completed before DAA therapy is begun (Chopra, 2023; Ito & Ngyuen, 2023). The DAA therapy regimens for patients who have HCV and HCC are no different than those for the general population (Chopra & Arora, 2024a).

Patients who did not have a 12-week SVR can be re-treated, and there are several options (Bhattacharya et al., 2023; Graf et al., 2024).

Vosevi® is a combination of voxilaprevir, velpatasvir, and sofosbuvir that has labeled uses for treating:

1. Patients who have genotype 1, 2, 3, 4, 5, or 6 and who were treated with a regimen that included an NS5A inhibitor, and
2. Patients who have genotype 1a or 3 and have been treated with a regimen that included sofosbuvir but not an NS5A inhibitor (Vosevi, 2019).

Other recommended DAA regimens are listed below (Bhattacharya et al., 2023).

1. Sofosbuvir-based treatment failure without cirrhosis or with compensated cirrhosis.
   1. Genotypes 1 to 6: Sofosbuvir/velpatasvir/voxilaprevir, 12 weeks. For genotype 3 infection with compensated cirrhosis, add weight-based ribavirin if there are no contraindications.
   2. Genotypes 1, 2, 4, 5: Glecaprevir/pibrentasvir, 16 weeks. This regimen is not recommended for patients with prior exposure to an NS5A inhibitor plus NS3/4A protease inhibitor regimen, e.g., elbasvir and grazoprevir.
      1. Note: Ribavirin is a nucleoside anti-HCV drug; it was used with interferon in the first several iterations of HCV treatment.
2. Glecaprevir/pibrentasvir treatment failure without cirrhosis or with compensated cirrhosis.
   1. Genotypes 1-6: Glecaprevir/pibrentasvir +sofosbuvir + weight-based ribavirin, 16 weeks.
   2. Genotypes 1-6: Sofosbuvir/velpatasvir/voxilaprevir, 12 weeks.  For patients with compensated cirrhosis, adding weight-based ribavirin is recommended.
3. Sofosbuvir/velpatasvir/voxilaprevir or sofosbuvir + glecaprevir/pibrentasvir treatment failure without cirrhosis or with compensated cirrhosis.
   1. Genotypes 1-6: Glecaprevir/pibrentasvir + sofosbuvir + weight-based ribavirin, 16 weeks. Twenty-four weeks of treatment should be considered for extremely difficult cases like genotype 3 infection with compensated cirrhosis or failure of the sofosbuvir + glecaprevir/pibrentasvir therapy.
   2. Genotypes 1-6: Sofosbuvir/velpatasvir/voxilaprevir + weight-based ribavirin, 24 weeks.
4. Sofosbuvir- or NS5A inhibitor-based treatment failure with decompensated cirrhosis.
   1. Genotypes 1-6: Sofosbuvir/velpatasvir + weight-based ribavirin, 24 weeks. A low starting dose initial dose of ribavirin ─ 600 mg ─ is recommended for patients with CTP class C cirrhosis. The dose can be increased as tolerated.
   2. Genotypes 1, 4, 5, 6: Ledipasvir/sofosbuvir + weight-based ribavirin, 24 weeks. A low starting initial dose of ribavirin ─ 600 mg ─ is recommended for patients with CTP class C cirrhosis. The dose can be increased as tolerated.

Transmission of the virus: Patients should be instructed not to share personal care items like toothbrushes and razors that may be contaminated with blood.

Sexual transmission of HCV between monogamous heterosexual partners who are not IV drug users appears very uncommon, and barrier protection is not recommended. Patients should be counseled on safe sex practices, and they should be given information on how hepatitis C is transmitted and instructed on how to avoid transmission of the virus.

People who have multiple sexual partners and MSM should be encouraged to use condoms.

Injection drug users should be advised not to share needles or injection drug equipment.

HCV is not transmitted by casual physical contact, coughing, food or water, sneezing, or sharing eating utensils.

Alcohol: No amount of alcohol has been established as safe for patients who have hepatitis C. Excess alcohol consumption can cause cirrhosis, and it has been strongly associated with the development and progression of fibrosis and hepatocellular cancer. Patients should be advised to abstain from drinking alcohol, and patients who have an alcohol use disorder should be referred for treatment.

Drug-drug interactions: Patients should be told that drug-drug interactions can negatively influence the effectiveness of DAAs, and potentially significant interactions can occur between over-the-counter medications and dietary/herbal supplements and DAAs. Do not take a new medication or supplement without informing the provider or another healthcare professional.

Patients who take antidiabetic medications or warfarin should be instructed that the antiviral medications can cause hypoglycemia or hyperglycemia and can reduce the anticoagulant effects of warfarin.

Employment: People who have hepatitis C should not be restricted from employment. Infected healthcare workers need only to follow infection control procedures and use Standard Precautions.

Marijuana: Patients should be advised to abstain from using marijuana.

Medications: Patients should not take an over-the-counter medication, dietary supplement, or herbal product unless their provider or healthcare professional determines that doing so is safe.

Obesity: Patients who are obese should be advised to lose weight.

Reinfection: An SVR does not provide immunity against reinfection with hepatitis C, either from the same genotype or the other genotypes. Patients should be instructed to contact their provider or another healthcare professional if they may have been reinfected.

Smoking: Smoking cessation should be encouraged.

Substance use: Patients who are IV drug users have a significant risk of infection and reinfection. These patients should be referred to a SUD treatment program and have routine follow-up laboratory testing (Ghany et al., 2020).

Treatment adherence: Patients should be advised that non-compliance with the treatment regimen could cause treatment failure.

Treatment - Adverse effects: The adverse effects of the direct-acting antivirals are mild and usually well tolerated. Patients should be instructed to contact their provider or another healthcare professional if they have any signs or symptoms that are new, unusual, severe, intolerable, or that interfere with activities of daily living. They should contact their healthcare provider or another healthcare professional if they develop any signs or symptoms indicative of liver damage.

The genetic diversity and rapid rate of mutation have prevented the development of an HCV vaccine (Dienstag, 2022a), and there is no effective prophylactic treatment for acute exposures like a needle stick (Feld, 2022; National Clinician Consultation Center, 2021). The CDC's recommendations for acute, discrete, and possible exposures to HCV, like a needle stick, are listed below (Moorman et al., 2020).

1. The source's HCV status should be determined by an HCV RNA test (preferable) or an anti-HCV antibody test, and if that is positive, with a confirmatory HCV RNA test.
2. The exposed person's HCV status should be determined with an HCV RNA test. This should be done as soon as possible, preferably within 48 hours.
3. If the source was HCV RNA positive or anti-HCV was positive, but HCV RNA was not obtained, or if the source's HCV status can't be determined, the exposed person should have an HCV RNA test done at three to six weeks post-exposure.
4. If the HCV RNA is positive, the exposed person should be referred to care.
5. If the HCV RNA test is negative, the exposed person should have an anti-HCV antibody test done at four to six months post-exposure.

Nursing care for patients who have HCV has been greatly simplified by the use of up-to-date DAAs. The course of therapy has been reduced from 44 weeks to 12 weeks, the risk of serious drug-induced complications has been dramatically reduced, and unlike interferon-based regimens, the side effects of these drugs are mild and well-tolerated.

These changes mean that the focus of nursing care for patients who have HCV has, to a large degree, shifted from physical care to education and support: education about lifestyle issues relevant to HCV and support that helps and encourages patients to make the changes that are necessary for continued good health.

Nursing care for a patient who has HCV will involve:

• Knowledge of the extrahepatic complications of HCV.
• Knowledge of the signs, symptoms, and complications of cirrhosis.
• Knowledge of the medications and their potential side effects.
• Patient education, specifically about extrahepatic complications of HCV and the safe and effective use of antiviral drugs.
• Patient education, specifically about the risks of alcohol use/abuse, diabetes, obesity, and smoking, about HCV.
• Support and education, specifically about the beneficial effects of alcohol abstinence, exercise, smoking cessation, and weight loss about HCV.
• Assess the patient's level of knowledge regarding HCV transmission and behaviors that can put them at risk for reinfection.

HCV is a chronic liver infection that can cause liver damage, cirrhosis, and liver cancer, and HCV can also cause serious extrahepatic complications in essentially every organ system. HCV is one of the most common bloodborne diseases in the United States. HCV is an important cause of liver cancer; it may be a contributing cause of many common chronic diseases.

The HCV was first isolated and identified in 1989. For many years, the available treatments were lengthy, i.e., almost one year of drug therapy, not highly effective, and they caused very unpleasant and occasionally very serious adverse effects. DAAs have decreased the incidence of chronic HCV infections and offered a cure rate of 95% to 100%, the treatment regimens are much shorter, and the drugs are well tolerated.

However, HCV is still a major public health problem, and the continued use of illicit drugs and the opioid epidemic have contributed to the persistence of a disease that can be cured. Another issue that contributes to the failure to eliminate HCV is the nature of the disease. Chronic HCV seldom causes signs and symptoms, and the disease progresses silently for decades, so many infected people do not know they have HCV. Also, the progression of liver fibrosis and liver damage caused by HCV is negatively affected by comorbidities and common lifestyle issues like alcohol abuse, obesity, and smoking.

Fortunately, the treatment of HCV has been greatly simplified. The currently available direct-acting antivirals are highly effective. The treatment regimens typically use oral medications taken once a day for 12 weeks, and serious adverse effects are uncommon. Simplified treatment plans that can be initiated and monitored by physicians, advanced practice registered nurses, and nurse practitioners are easily available. In many cases, HCV can be cured, liver damage can be prevented, or if it is present, it can be reversed, and extrahepatic complications can be prevented and reversed.

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